Vaccine development alone may not be sufficient to protect the U.S. against bioterrorist attack with smallpox, especially against an engineered virus containing an IL4 gene. Major vulnerabilities remain, even with a well-organized vaccination program in place, including mass disruption caused by fear of an epidemic and the morbidity and mortality of a nationwide smallpox vaccination program. Therefore, in response to the RRGP-BTRR request for "new prevention strategies for those at risk of exposure," we propose to investigate the effectiveness of ultraviolet (254 nm) germicidal irradiation (UVGI) as a strategy for preventing dissemination of variola major virus in hospitals and other public buildings. As a prevention strategy air sanitation has several important attributes: it can be deployed safely before an outbreak; it can build public confidence; it can limit the growth of an outbreak during the critical period prior to identification of the outbreak and the start of a vaccination campaign; and it can have public health benefits even if an attack with smallpox never occurs by reducing spread of other airborne infections. In this project, we will use a low virulence vaccinia virus strain, provided by Acambis Corp., as a simulant for variola major. Initial experiments will be performed in a small aerosol chamber to validate sampling and analysis methods and to determine the UVGI induced exponential decay constants for vaccinia as a function of droplet nuclei size and relative humidity. Then, we will simulate "real world" conditions in a hospital room size chamber (4.5 m x 3 m x 2.9 m) to determine the utility of upper room UVGI for elimination of poxvirus aerosols. Aerosolized virus will be collected in a liquid swirling sampler and a cascade impactor and cultured to determine infectivity. Upper-room UVGI can potentially lower the concentration of infective organisms in the lower part of the room and thereby control the spread of airborne infections among room occupants, without exposing occupants to a significant amount of UV. This work will provide a sound scientific basis for decisions on whether to recommend wide spread implementation of upper room UVGI in hospitals and public buildings as a first line of defense against smallpox and other bioengineered airborne communicable infections.